Inhaled ammonium persulphate inhibits non-adrenergic, non-cholinergic relaxations in the guinea pig isolated trachea.

BACKGROUND: Persulphates can act both as irritants and sensitizers in inducing occupational asthma. A dysfunction of nervous control regulating the airway tone has been hypothesized as a mechanism underlying bronchoconstriction in asthma. OBJECTIVES: It was the aim of this study to investigate whether inhaled ammonium persulphate affects the non-adrenergic, non-cholinergic (NANC) inhibitory innervation, the cholinergic nerve-mediated contraction or the muscular response to the spasmogens, carbachol or histamine, in the guinea pig epithelium-free, isolated trachea. METHODS: Male guinea pigs inhaled aerosols containing ammonium persulphate (10 mg/m(3) for 30 min for 5 days during 3 weeks). Control animals inhaled saline aerosol. NANC relaxations to electrical field stimulation at 3 Hz were evaluated in whole tracheal segments as intraluminal pressure changes. Drugs inactivating peptide transmission, nitric oxide synthase, carbon monoxide production by haem oxygenase-2 and soluble guanylyl cyclase were used to assess the involvement of various inhibitory neurotransmitters. Carbachol and histamine cumulative concentration-response curves were obtained. RESULTS: In both groups, nitric oxide and carbon monoxide participated to the same extent as inhibitory neurotransmitters. In exposed animals, the tracheal NANC relaxations were reduced to 45.9 +/- 12.1% (p < 0.01). The cholinergic nerve-mediated contractions to electrical field stimulation and the muscular response to histamine were not modified by ammonium persulphate exposure. The muscular response to carbachol was unaffected up to 1 microM. Conversely, the response to the maximal concentration of carbachol (3 microM) was increased (p < 0.01). CONCLUSION: Ammonium persulphate inhalation at high concentrations impairs the nervous NANC inhibitory control in the guinea pig airways. This may represent a novel mechanism contributing to persulphate-induced asthma.

Role of carbon monoxide in electrically induced non-adrenergic, non-cholinergic relaxations in the guinea-pig isolated whole trachea.

BACKGROUND AND PURPOSE: Nitric oxide (NO) and vasoactive intestinal peptide (VIP) are considered transmitters of non-adrenergic, non-cholinergic (NANC) relaxations in guinea-pig trachea, whereas the role of carbon monoxide (CO) is unknown. This study was designed to assess the participation of CO, and to investigate the localization of haem oxygenase-2 (HO-2), the CO-producing enzyme, in tracheal neurons. EXPERIMENTAL APPROACH: NANC responses to electrical field stimulation (EFS) at 3 and 10 Hz were evaluated in epithelium-free whole tracheal segments as intraluminal pressure changes. Drugs used were: L-nitroarginine methyl ester (L-NAME, 100 microM) to inhibit NO synthase (NOS), alpha-chymotrypsin (2 U ml(-1)) to inactivate VIP, zinc protoporphyrin-IX (ZnPP-IX, 10 microM) to inhibit HO-2, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM), a soluble guanylyl cyclase inhibitor. For immunohistochemistry, tissues were exposed to antibodies to PGP 9.5, a general neuronal marker, HO-2 and NOS, and processed with an indirect immunofluorescence method. KEY RESULTS: alpha-Chymotrypsin did not affect NANC relaxations. ODQ inhibited NANC responses by about 60%, a value similar to that obtained by combining L-NAME and ZnPP-IX. The combination of ODQ, L-NAME and ZnPP-IX reduced the responses by 90%. Subpopulations of HO-2 positive neurons containing NOS were detected in tracheal sections. CONCLUSIONS AND IMPLICATIONS: In the guinea-pig trachea, NANC inhibitory responses at 3 and 10 Hz use NO and CO as main transmitters. Their participation is revealed following inhibition of NOS, HO-2 and soluble guanylyl cyclase. The involvement of CO as a relaxing transmitter paves the way for novel therapeutic approaches in the treatment of airway obstruction.

[Exposure to ammonium persulphate by inhalation: effect on the NANC inhibitory neurotransmitters in the guinea pig trachea]. / Esposizione inalatoria a persolfato d'ammonio: effetto sulle componenti del sistema NANC inibitorio della trachea di cavia.

To evaluate the effect of ammonium persulphate (AP) inhalation on NANC inhibitory (i-NANC) neurotransmitters of guinea pig airways, we exposed eight guinea pigs to AP (1 mg/m3), by aerosol inhalation for 30 minutes daily for three weeks. Control animals inhaled saline aerosol. After the last exposure, the isolated trachea was mounted in an organ bath and electrically stimulated in the presence of hyoscine, piperoxane and propranolol. The i-NANC responses were evaluated as decreases in intraluminal pressure and expressed as area under the curve (AUC, Pa x seconds). The isolated tracheae were treated with a-chymotrypsin, L-NAME, zinc protoporphyrin IX and ODQ, that inhibit the production or action of the single neurotransmitters, like peptides, NO and CO. In the exposed individuals, the NANC relaxations were below 50%, as compared to controls (P < 0.01). NO and CO were the neurotransmitters responsible for all the i-NANC responses, in similar proportions either in exposed individuals or in controls. In conclusion, ammonium persulphate exposure impairs the i-NANC control of airway tone without specifically affecting any neurotransmitter.

Identification of galanin receptor 1 on excitatory motor neurons in the guinea pig ileum.

Exogenously administered galanin inhibits cholinergic transmission to the longitudinal muscle and reduces peristaltic efficiency in the guinea pig ileum with a mechanism partially mediated by galanin receptor 1 (GAL-R1). We investigated the effect of exogenous galanin 1-16, which has high affinity for GAL-R1, on the ascending excitatory reflex of the circular muscle elicited by radial distension in isolated segments of guinea pig ileum. We used a three-compartment bath that allows dissecting the ascending pathway into the oral (site of excitatory motor neurons), intermediate (site of ascending interneurons) and caudal compartment (site of intrinsic primary afferent neurons). Galanin 1-16 (0.3-3 micromol L(-1)) applied to the oral compartment inhibited in a concentration-dependent manner the ascending excitatory reflex elicited by the wall distension in the caudal compartment. This effect was antagonized by the GAL-R1 antagonist, RWJ-57408 (1 and 10 micromol L(-1)). By contrast, galanin 1-16 was ineffective when added to the intermediate or caudal compartment up to 3 micromol L(-1). GAL-R1 immunoreactive neurons did not contain neuron-specific nuclear protein, a marker for intrinsic primary afferent neurons. These findings indicate that GAL-R1s are present on motor neurons responsible for the ascending excitatory reflex, but not on ascending interneurons and intrinsic primary afferent neurons.

Features and severity of occupational asthma upon diagnosis: an Italian multicentric case review.

BACKGROUND: The severity of occupational asthma (OA) at the time of diagnosis is not known. In this study we aimed to evaluate some features of the disease at the time of diagnosis, particularly looking at severity and treatment before diagnosis. METHODS: Medical records of subjects (n = 197) who had received a diagnosis of OA in six specialized centres of Northern and Central Italy in the period 1992-97 were reviewed. The severity of the disease at the time of diagnosis was determined on the basis of symptoms, peak expiratory flow (PEF, percentage predicted), forced expiratory volume in one second (FEV1, percentage predicted), and PEF variability, following the criteria of the National Institutes of Health and World Health Organizaton (NIH/WHO) guidelines on asthma. Medications used in the month before diagnosis were recorded. RESULTS: The most common etiological agents were isocyanates (41.6%), flours (19.8%), woods (9.7%) and natural rubber latex (7.6%). The level of asthma severity (AS) was mild intermittent in 23.9% patients, mild persistent in 28.9%, moderate in 41.6%, and severe in 5.6%. Asthma severity was positively associated with current or previous smoking (P < 0.05), and was not related to atopy and current exposure. A relationship with bronchial reactivity to methacholine was shown in subjects at work. Treatment before diagnosis was consistent with the NIH/WHO guidelines in only 13.2% patients, whereas 75.6% were undertreated and 11.2% were overtreated. CONCLUSIONS: In this study we found that the majority of patients had mild asthma at the time of diagnosis and that cigarette smoking was associated with a greater severity. Moreover, the majority of patients were undertreated before etiological diagnosis.

[Respiratory occupational allergies: the experience of the Hospital Operative Unit of Occupational Medicine in Lombardy from 1990 to 1998]. / Allergopatie professionali respiratorie: l'esperienza delle Unità Operative Ospedaliere di Medicina del Lavoro in Lombardia dal 1990 al 1998.

A retrospective study on occupational rhinitis and asthma diagnosed in 7 occupational health institutes in Lombardia (North-West Italy) was performed using a standardized card. 141 cases of rhinitis and 281 cases of asthma due to sensitization to occupational agents were analyzed and their clinical characteristics, aetiology, diagnostic methods and associated allergic diseases were determined. In this population the most frequent agents of occupational rhinitis were wheat flour and latex, whereas those of occupational asthma were latex and isocyanate. More than half of the subjects had more than one clinical manifestation of allergy. In 92 out of the 281 asthmatic patients rhinitis was the first clinical manifestation, particularly in subjects sensitized to high molecular weight substances, and preceded, asthma by 12 months as a mean. Specific bronchial provocation tests were useful for the diagnosis of asthma in 153 of the asthmatic patients and 45 of them had an isolated late bronchial reaction following the specific stimulus. At diagnosis 61 subjects (21.7%) had FEV1 < 80% of predicted; factors associated to ventilatory impairment were sensitization to high molecular weight substances, duration of exposure to the sensitizing agent, persistence of exposure after onset of symptoms.

A respiratory and allergy survey in textile workers employed in early stages of wool processing.

OBJECTIVES: To determine frequency and type of respiratory and allergic symptoms in textile workers employed in early stages of wool processing. METHODS: A cross-sectional study was carried out in four wool textile mills. 202 subjects (n. 148 males, 54 females, mean age 38.9 yrs, SD 9.5) employed in early stages (combing, n. 138, carding, n. 64) of wool processing were examined and an environmental survey was carried out to determine the level of wool dust exposure. All subjects were submitted to clinical interview, spirometry and measurement of serum specific IgE (s-IgE) against extracts of two wool lots (Australia and New Zealand) by means of RAST. In the subjects with a positive questionnaire for allergic symptoms serum specific IgE for common pneumoallergens were measured (PHADIATOP test). RESULTS: We found higher air dust concentrations during carding operations (inspirable fraction-IF-: range 1.6-20 mg/m3; respirable fraction (RF): 0.5-6.9 mg/m3) and lower concentrations during combing (IF 0.3-0.7 mg/m3, RF 0.1-0.3 mg/m3). 70 out of 202 subjects (34.7%, n. 26 employed in carding and n. 44 in combing operations) reported work-related symptoms. Cutaneous itching was reported by 30 subjects, upper airway irritation by 24, ocular irritation by 17 and dyspnoea by 5. Globally 27 subjects (13.4%) had respiratory work-related symptoms. 12 subjects reported only seasonal respiratory symptoms not related to work. Within the group of 82 symptomatic subjects, 62 (75.6%) had serum specific IgE for common pneumoallergens. In the whole group (n. 202) mean basal FEV-1 was L 3.6, SD 0.9 (103.6% of predicted values). No significant difference was found in basal FEV-1 between carding and combing workers. No s-IgE against the two wool extracts was detectable in any of the 202 examined subjects. CONCLUSIONS: Our data show that in early stages of wool processing: 1) the overall frequency of respiratory work-related symptoms is low and does not seem to be related to the stages of processing, 2) symptoms are mainly nasal and/or ocular; 3) serum s-IgE against wool extracts are not detectable. We conclude that respiratory allergy risk in wool textile mills is low.

Occupational asthma: a longitudinal study on the clinical and socioeconomic outcome after diagnosis.

AIM: To evaluate the clinical outcome and socioeconomic consequences of occupational asthma (OA). SUBJECTS AND METHODS: Twenty-five patients with OA both to high- and low-molecular-weight agents (3 and 22, respectively) confirmed by specific inhalation challenge were followed up for 12 months after the diagnosis. Upon diagnosis, each patient received a diary on which to report peak expiratory flow rate (PEFR), symptoms, drug consumption, expenses directly or indirectly related to the disease, as well as information regarding personal socioeconomic status. At each follow-up visit (1, 3, 6, and 12 months), the patients underwent clinical examination, spirometry, methacholine (Mch) challenge, and assessment of diary-derived parameters and socioeconomic status. Asthma severity (AS) was classified into four levels, based on symptoms, drug consumption, and PEFR variability. RESULTS: At 12 months, 13 patients (group A) had ceased exposure; the remaining 12 patients (group B) continued to be exposed. At diagnosis, FEV1 percent and provocative dose causing a 20% fall in FEV1 (PD20) of Mch were lower in group A than in group B; patients of group A were also characterized by significantly higher basal AS levels. At 12 months, no significant variation in FEV1 percent or PD20 was found for either group, while AS levels improved in both groups, the change being more marked for group A than group B. Pharmaceutical expense at 12 months significantly (p < 0.05) decreased, as compared with the first month, in group A, whereas it tended to increase in group B. In group A, 9 of 13 subjects had reported a deterioration of their socioeconomic status as compared with 2 of 12 in group B (p < 0.01). A significant loss of income was registered in patients of group A (median 21.45, 25th to 75th percentiles 16.9 to 25.8 Italian liras x 10(6) on the year preceding diagnosis and 15.498, 10.65 to 21.087 Italian liras x 10(6) on the year after diagnosis; p < 0.01), whereas no significant change was seen for patients in group B. CONCLUSIONS: In OA, cessation of exposure to the offending agent results in a decrease in asthma severity and in pharmaceutical expenses, but it is associated with a deterioration of the individual's socioeconomic status (professional downgrading and loss of work-derived income). There appears to be a great need for legislation that facilitates the relocation of these patients.

[Epicutaneous sensitization to metals and contact allergic dermatitis: analysis of an ambulatory caseload]. / Sensibilizzazione epicutanea a metalli e dermatite allergica da contatto: analisi di una casistica ambulatoriale.

We have retrospectively analyzed the clinical and anamnestic features of 233 out-patients (197 females and 36 males; mean age: 33 years; SD: +/- 13.3) with epicutaneous sensitization to metals, who had been examined at the department of allergology of our institution during one year. Among females, nickel sulphate was the metallic salt which most frequently resulted positive at patch testing (87.8% of cases), followed by cobalt chloride (23.6%) and potassium bichromate (10.2%). Nickel was the most common sensitizing metal also in males (58.3%), among whom sensitization to chromate resulted second in order of frequency (30.6%), and sensitization to cobalt was relatively rare (11.1%). In selected cases, the utilization of additional, specific series allowed to document rare cases of sensitization to metallic salts not included in the standard patch test series (copper sulphate, cadmium chloride, zinc stearate, phenylmercuric nitrate). 78 patients were sensitized to more than one metal. Skin sensitivity to metals was often linked to allergic disease familiarity and/or to sensitization toward type I allergens. Allergic contact dermatitis was diagnosed in 80 patients: cutaneous manifestations had been present on average for over four years, sometimes in generalized or persistent form. An occupational contact with the causative metals was identified in 15 cases. However, the occupational origin of the disease could never be documented with certainty, due to concomitance of frequent non-occupational exposures and to lack of information on pre-employment skin sensitivity status. Thus, the value of patch testing, during both pre-employment screening and health surveillance, is emphasized.

Occupational asthma and rhinitis caused by 1,2-benzisothiazolin-3-one in a chemical worker.

We report a case of occupational asthma and rhinitis caused by inhalation of 1,2-benzisothiazolin-3-one, an additive used as a microbicidal in detergent production, in a 26-year-old man employed in a chemical factory producing detergents. The subject's task consisted of pouring raw materials into the recipient of a machine which mixed the substances. Two months after the beginning of this job the patient complained of rhinitis and asthma at the workplace. The specific challenge test with 1,2-benzisothiazolin-3-one, one of the raw materials to which the subject was exposed, provoked an immediate prolonged asthmatic response and nasal symptoms, whereas exposure to other agents (e.g., alpha-amylase, alcalase or bezalkonium chloride) to which the patient was also exposed at work did not. To our knowledge this is the first case of occupational asthma and rhinitis caused by this compound.

Bronchial responsiveness to ultrasonic "fog" in occupational asthma due to low molecular weight chemicals.

BACKGROUND: In a previous work we have demonstrated that the use of an indirect stimulus such as ultrasonically nebulized distilled water (UNDW, "fog") challenge, in addition to methacholine, in the assessment of occupational asthma due to TDI improves our ability in detecting sensitized subjects. OBJECTIVE: In the present study we aimed to determine the validity of "fog" in the assessment of occupational asthma induced by various low molecular weight substances. METHODS: Fourty subjects exposed to low molecular weight substances with work-related respiratory symptoms underwent methacholine, UNDW and specific bronchial challenge tests. Diagnosis of occupational asthma was made in 20 of 40 patients who developed bronchoconstrictive responses to the specific challenges (reactors). Sensitivity and specificity of UNDW alone, of methacholine alone, and of the combination of the two tests were determined at two different cutpoints of PD20FEV1 of methacholine, with the results of the specific challenge as the "gold standard". RESULTS: Frequency and severity of bronchial hyperresponsiveness both to UNDW and to methacholine were significantly higher in reactors than in nonreactors. Ultrasonically nebulized distilled water had higher specificity (80% versus 60%) but lower sensitivity (65% versus 75% to 90%) than methacholine. As compared with methacholine alone, the combination in series of the two challenges (both challenges positive) substantially improved specificity (85% versus 60%). CONCLUSIONS: In conclusion, in the assessment of low molecular weight chemical-induced asthma diagnosed with the specific challenge as the "gold standard," UNDW challenge proves more specific than methacholine for occupational asthma, but it is considerably less sensitive. The combination of the two challenges results in very high sensitivity and high specificity for occupational asthma, therefore, although further investigations are required for the definitive diagnosis, it should be regarded as a useful means to confirm objectively a suggestive history.

Occupational asthma, rhinitis and urticaria due to piperacillin sodium in a pharmaceutical worker.

A 28 year old man with no history of atopy was referred to our hospital for possible work-related asthma. He had been employed in the production section of a pharmaceutical company for 2 yrs, and in the last 2 months he had complained of dyspnoea, wheezing, chest tightness, symptoms of rhinitis and a cutaneous rash when exposed to powdered antibiotics. Symptoms disappeared after being transferred to the packaging section. When the subject was admitted to our department he was asymptomatic. Basal lung function tests were in the normal range. Bronchial challenges with methacholine and with ultrasonically-nebulized distilled water were negative. Skin-prick test with piperacillin sodium gave a strong positive response at a very low concentration. Specific inhalation challenge with piperacillin sodium resulted in an immediate asthmatic reaction, and also reproduced rhinitis symptoms and the cutaneous rash. A control challenge with lactose, and the specific challenge test with cefuroxime sodium (another antibiotic to which the patient was exposed at the workplace) were negative. We conclude that piperacillin sodium is an agent that can cause occupational asthma.

Bronchial responsiveness to ultrasonic fog in occupational asthma due to toluene diisocyanate.

To determine the validity of ultrasonic nebulization of distilled water (UNDW, "fog") in comparison with methacholine challenge, in the assessment of toluene diisocyanate (TDI) asthma, we evaluated 75 subjects exposed to TDI with work-related respiratory symptoms. Subjects were submitted to bronchial challenge with methacholine at first, thereafter to UNDW inhalation and to specific challenge with TDI. The diagnosis of TDI-asthma was made in 30 of 75 patients (40 percent) who developed a bronchoconstrictive response to the specific challenge (reactors). Sensitivity and specificity of UNDW alone, methacholine alone, and of the combination of the two tests were determined with the results of the specific challenge with TDI as the "gold standard." Both frequency and severity of bronchoconstrictive response to UNDW (FEV1 decrease > or = 15 percent) and the degree (PD15 FEV1) and frequency of bronchial hyperresponsiveness to methacholine were significantly higher in TDI reactors than in nonreactors. The UNDW had higher specificity (82.2 percent vs 51.1 percent) but lower sensitivity (40 percent vs 76.7 percent) than methacholine. The combination in parallel (positivity of any of the two challenges) of methacholine and UNDW challenge did not change sensitivity to a great extent (80 percent vs 76.7 percent), whereas combination in series (positivity of both challenges) had considerably greater specificity (86.7 percent vs 51.1 percent) than methacholine alone. We conclude that in the assessment of TDI-asthma, the validity of UNDW challenge alone is limited since it is insufficiently sensitive. Instead, combining UNDW and methacholine challenge when methacholine is positive improves our ability in identifying subjects with TDI-asthma diagnosed with the specific challenge. This procedure constitutes a first objective confirmation of a suggestive history of TDI-asthma that is useful for clinical purposes. However, especially for medicolegal purposes, the definitive diagnosis requires the specific challenge.

Bronchial reactivity to methacholine in HIV-infected individuals without AIDS.

To evaluate bronchial reactivity to methacholine in human immunodeficiency virus (HIV) infection, we submitted 25 HIV-seropositive subjects without full-blown AIDS and 25 HIV-seronegative subjects, all inmates in a drug rehabilitation center for previous intravenous drug abuse, to interview and to bronchial challenge with methacholine. Four (16 percent) HIV-seropositve and three (12 percent) HIV-seronegative subjects noted bronchospastic symptoms. Baseline FEV1 and MEF50 percent were within the normal range in every patient. Bronchial hyperreactivity to methacholine (PD20FEV1 < 1,400 micrograms) was found in two (8 percent) HIV-seropositive and in four (16 percent) HIV-seronegative subjects, with no significant difference in the frequency between the two groups. We conclude that HIV infection without AIDS in intravenous drug users does not appear to be associated with an increased frequency of bronchospastic disorders and to bronchial hyperreactivity to methacholine.

Peak expiratory flow monitoring and airway response to specific bronchial provocation tests in asthmatics.

To assess the validity of peak expiratory flow (PEF), measured by means of a peak flow meter, in comparison to forced expiratory volume in one second (FEV1) for measuring the airway response during specific bronchial challenges, we registered PEF and FEV1 in a random sequence during 75 positive (decrease in FEV1 of > or = 15% from baseline) and 75 negative (decrease in FEV1 < 15% from baseline) challenges with chemicals or allergens. The correlation between PEF and FEV1 in terms of absolute values and of percentage of change from baseline was statistically highly significant (p < 0.001) in all challenges and in the different pattern of response, immediate, dual and late. Relative operating characteristic analysis showed that an absolute decrease in PEF of > or = 70 l.min-1 in the immediate and of > or = 80 l.min-1 in the late phase of the response (cut-off points) gave optimal discrimination between challenges with a bronchoconstrictive response (defined as a FEV1 decrease > or = 15% from baseline), and challenges without. These cut-off points, however, were highly specific (92 and 93.3%, respectively), but not as sensitive (70.6 and 61.1%, respectively), and smaller absolute changes in PEF from baseline do not exclude a bronchoconstrictive response. Our data suggest that PEF readings are a useful diagnostic tool in assessing the airway response during a specific bronchial challenge in asthmatics, although with some limitations. PEF readings can be used to monitor the late response to a challenge during the evening and the night if PEF readings are carefully considered in relation to clinical symptoms.

Occupational asthma: fate and management after the diagnosis.

The clinical and socio-professional fate of subjects with occupational asthma is not univocal. We re-examined twenty-nine subjects diagnosed in our center as suffering from this disease an average 14 months, SE 1.54 after the diagnosis. At the follow-up examination each patient underwent interview, spirometry and methacholine challenge, 18 patients (group A) had ceased exposure to the sensitizing agent but among them only 7 had been relocated in another area of the plant, the others had resigned or retired. The other patients had not changed workplace, 7 (group B) having had intermittent exposure to the offending agent and 4 (group C) having continued to be exposed daily. At the follow-up examination only 9 patients were asymptomatic, each of them belonging to group A, whereas in the other 9 of the same group symptoms persisted, although reduced. In group B and C all patients were still symptomatic and required pharmacologic treatment. Within group A patients who became asymptomatic had shorter duration of symptoms before diagnosis (12.9 months, SE 6.4 vs 23.9, SE 9.7), higher FEV-1 (96.1, SE 6.7 vs 86.9, SE 5.6) and PD20FEV-1 (1773.4 micrograms, SE 590 vs 730.8, SE 295) at the time of the diagnosis and showed a significant (p < 0.01) increase in FEV-1 (from 96.1, SE 6.2 to 101.6, SE 5.5) and a tendency to decrease in bronchial reactivity to methacholine at the follow-up examination. At the time of the follow-up examination only 5 out of 29 patients (17.2%) had been contacted by the compensation board.(ABSTRACT TRUNCATED AT 250 WORDS)

Local immunotherapy by inhalation of a powder extract in asthma due to house dust mite Dermatophagoides pteronyssinus: a double-blind comparison with parenteral immunotherapy.

To verify the efficacy and the tolerability of local immunotherapy (LI) by inhalation of a powder extract of house dust mite (HDM), in comparison with parenteral immunotherapy (PI) by injection, 10 patients with asthma due to HDM were studied in a blind fashion. 5 patients (Group A) underwent LI and subcutaneous injections of placebo, 5 patients (Group B) underwent PI and inhalation of lactose for 6 months. In both groups each inhalation was preceded by premedication with disodium cromoglycate (DSCG) (40 mg). In Group A a significant decrease in symptoms score and in peak expiratory flow (PEF)-derived parameters was observed already after 3 months of treatment, and 2 patients lost the late component of the bronchial response to the challenge with HDM. No significant variation was found in bronchial responsiveness to methacholine and ultrasonically nebulized distilled water (UNDW) and in immunologic humoral and cellular parameters in peripheral blood after treatment in either group. No local important adverse reactions were observed in Group A and no systemic side effects were observed in either group. We conclude that LI is as effective as PI, but more rapid in its action, in the treatment of asthma due to HDM. Moreover, LI is locally well tolerated, providing DSCG is inhaled before each therapeutic inhalation, and does not induce systemic side effects.

Toluene diisocyanate-induced asthma: clinical findings and bronchial responsiveness studies in 113 exposed subjects with work-related respiratory symptoms.

We report the clinical findings and the results of inhalation challenge with toluene diisocyanate (TDI) and methacholine in 113 subjects with a history of exposure to TDI and work-related respiratory symptoms. Only some of the subjects (40.7%) had isocyanate asthma, diagnosed by a positive TDI inhalation challenge. Most reactors had a dual (30.4%) or a late (41.3%) response. The interval between the last occupational exposure and the specific challenge was significantly shorter in reactors, and among this group the number of immediate reactions to TDI decreased progressively with an increasing interval. The reactors had a significantly higher proportion of positive responses to methacholine and a significantly lower mean PD15 FEV-1 (provocative dose of methacholine which provoke a 15% decrease in forced expiratory volume in 1 second) (reactors: 557 micrograms, SEM 92.3; nonreactors: 1346 micrograms, SEM 128, P less than .01). Methacholine challenge could not identify subjects with isocyanate asthma.

Inhaled furosemide prevents both the bronchoconstriction and the increase in neutrophil chemotactic activity induced by ultrasonic "fog" of distilled water in asthmatics.

Inhaled furosemide has been shown to prevent bronchoconstriction induced by inhalation of ultrasonic nebulization of distilled water (UNDW) in bronchial asthma. To evaluate whether inhaled furosemide also prevents the increase in serum neutrophil chemotactic activity (NCA) observed during UNDW bronchoconstriction, we measured NCA during UNDW challenge without (control) and immediately after inhalation of furosemide (40 mg) or placebo (saline) in 10 asthmatics responsive to UNDW, in a randomized, double-blind study. NCA was assessed by measuring the maximal distance reached by neutrophils in a filter when challenged with the subject serum in a Boyden chamber ("leading front"). UNDW inhalation produced a significant increase in NCA in each subject. Gel filtration chromatography on S400 column indicated that the NCA released were 600 to 700 kD. Saline had no effect on bronchoconstriction nor on NCA increase induced by UNDW in nine patients. Furosemide did not change baseline FEV1, but it prevented bronchoconstriction and NCA increase in nine patients. In the whole group the maximal decrease in FEV1 after UNDW was -31.1%, SEM 4.7 after saline and -7.5%, SEM 5.2 after furosemide, p less than 0.001, the maximal increase in NCA after UNDW was +52.9%, SEM 9.2 after saline and +3.8%, SEM 3.1 after furosemide, p = 0.001. These results indicate that inhaled furosemide prevents both the bronchoconstriction and the NCA increase induced by UNDW inhalation in most asthmatic patients. This finding adds support to the suggestion that furosemide acts on mast cells.